Development Of Disease Research Articles

Non-obese lipedema patients show a distinctly altered quantitative sensory testing profile with high diagnostic potential.

Lipedema is a widespread severe chronic disease affecting mostly women. Characterized by painful bilateral fat accumulation in extremities sparing hands and feet, objective measurement-based diagnosis is currently missing. We tested for characteristic psychometric and/or sensory alterations including pain and for their potential for medical routine diagnosis. Pain psychometry was assessed using the German Pain Questionnaire. Sensory sensitivity toward painful and nonpainful stimuli was characterized in non-obese lipedema patients and matched controls using the validated quantitative sensory testing (QST) protocol of the German Research Network on Neuropathic Pain. Lipedema patients showed no overt psychometric abnormalities. Pain was reported as somatic rather than psychosomatic aversive. All QST measurements were normal, but the z-score of pressure pain thresholds (PPT) was twofold reduced and the z-score of vibration detection thresholds (VDT) was two and a half times increased. Both thresholds were selectively altered at the affected thigh but not the unaffected hand. Receiver operating characteristic analysis of the combination of PPT and VDT of thigh vs hand into a PVTH score (PPT, VDT, thigh, hand-score) shows high sensitivity and specificity, categorizing correctly 95.8% of the participants as lipedema patients or healthy controls. Bayesian inference analysis corroborated the diagnostic potential of such a combined PVTH score. We propose to assess PPT and VDT at the painful thigh and the pain-free hand. Combination in a PVTH score may allow a convenient lipedema diagnosis early during disease development.

Gestational diabetes mellitus and development of intergenerational non-alcoholic fatty liver disease (NAFLD) after delivery: a systematic review and meta-analysis

It is known that gestational diabetes mellitus (GDM)-complicated pregnancies could affect maternal cardiometabolic health after delivery, resulting in hepatic dysfunction and a heightened risk of developing non-alcoholic fatty liver disease (NAFLD). Hence, this study aims to summarise existing literature on the impact of GDM on NAFLD in mothers and investigate the intergenerational impact on NAFLD in offspring. Using 4 databases (PubMed, Embase, Web of Science and Scopus) between January 1980 and December 2023, randomized controlled trials and observational studies that assessed the effect of maternal GDM on intergenerational liver outcomes were extracted and analysed using random-effects meta-analysis to investigate the effect of GDM on NAFLD in mothers and offspring. Pooled odds ratio (OR) was calculated using hazards ratio (HR), relative risk (RR), or OR reported from each study, with corresponding 95% confidence intervals (CI), and statistical heterogeneity was assessed with the Cochran Q-test and I2 statistic, with two-sided p values. The study protocol was pre-registered on PROSPERO (CRD42023392428). Twenty studies pertaining to mothers and offspring met the inclusion criteria and 12 papers were included further for meta-analysis on intergenerational NAFLD development. Compared with mothers without a history of GDM, mothers with a history of GDM had a 50% increased risk of developing NAFLD (OR 1.50; 95% CI: 1.21-1.87, over a follow-up period of 16 months-25 years. Similarly, compared with offspring born to non-GDM-complicated pregnancies, offspring born to GDM-complicated pregnancies displayed an approximately two-fold elevated risk of NAFLD development (2.14; 1.57-2.92), over a follow-up period of 1-17.8 years. This systematic review and meta-analysis suggests that both mothers and offspring from GDM-complicated pregnancies exhibit a greater risk to develop NAFLD. These findings underline the importance of early monitoring of liver function and prompt intervention of NAFLD in both generations from GDM-complicated pregnancies. No funding was available for this research.

BRD4 promotes LPS-induced endothelial cells senescence via activating and cooperating STING-IRF3 pathway

Endothelial cells (ECs) senescence is closely associated with the initiation and development of multiple age-related cardiovascular diseases. It is necessary to explore the underlying molecular mechanisms of ECs senescence, which is not only the basis to decipher cellular senescence, but also a novel therapeutic target for the endothelial senescence-related diseases. BRD4, a key epigenetic regulator, is universally related to gene expression regulation and has been reported to accelerate cell senescence. Besides, emerging evidence has suggested that the stimulator of interferon genes protein (STING) can regulate inflammatory and senescence-related diseases. However, whether STING pathway activation is regulated by BRD4 in the context of ECs senescence remains largely unclear. Here, we observed that elevated BRD4 and activated STING-IRF3 signaling pathway during ECs senescence and further confirmed that BRD4 could abolish STING activation. We demonstrated that BRD4 could inhibit E3 ubiquitin ligase HRD1-mediated ubiquitination degradation of STING via inhibiting HRD1 transcription. In addition to the direct regulatory effect of BRD4 on STING activation, we have confirmed that BRD4 cooperates with IRF3 and P65 to promote SASP gene expression, thereby accelerating ECs senescence. Here, we proposed a novel mechanism underlying BRD4’ key dual role in activating the STING pathway during ECs senescence.

Analysis of potential Circular RNAs in regulating imatinib resistance of Gastrointestinal stromal tumor.

Recent studies have found that circular RNA is an abundant RNA species that belongs to part of the competing endogenous RNA network(ceRNA), which was proven to play an important role in the development, diagnosis and progress of diseases. However, the function of circRNAs in imatinib resistance in Gastrointestinal stromal tumor (GIST) are poorly understood so for. The present study aimed to screen and predict the potential circRNAs in imatinib resistance of GIST using microarray analysis. We determined the expression of circular RNAs in paired normal gastric tissues(N), primary GIST (gastrointestinal stromal tumor) tissues (YC) and imatinib mesylate secondary resistance GIST tissues(C) with microarray and predicted 8677 dysregulated circular RNAs. Compared with the YC group, we identified 15 circRNAs that were up-regulated and 8 circRNAs that were down-regulated in the C group. Gene ontology (GO)and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that these host linear transcripts that differentially express circular RNAs are involved in many key biological pathways, predicting the potential tumor-genesis and drug resistance mechanismrelated to HIF-1 pathway, later we draw the cirRNA-miRNA-mRNA network involved in the HIF-1 pathway and found several dysregulated circRNAs and the relationship between circRNA-miRNAs-mRNA, such as circRNA_06551, circRNA_14668, circRNA_04497, circRNA_08683, circRNA_09923(Green, down-regulation) and circRNA_23636, circRNA_15734(Red, up-regulation). Taken together, we identified a panel of dysregulated circRNAs that may be potential biomarkers even therapy relevant to the GIST, especially imatinib secondary resistance GIST.

Flavonoid and Chalcone Scaffolds as Inhibitors of BACE1: Recent Updates.

Flavonoids and chalcones are two major classes of chemical moieties that have a vast background of pharmacological activities. Chalcone is a subclass of flavonoids whose therapeutic potential has been implicated due to an array of bioactivities. A lot of research works have shown interest in investigating the neuroprotective effect of these molecules, and have revealed them to be much more potent molecules that can be used to treat neurodegenerative disorders. Beta-site APP cleaving enzyme (BACE1), which is majorly found in the brain, is one of the reasons behind the development of Alzheimer's disease (AD). Flavonoids and chalcones have proven clinical data that they inhibit the production of Aβ plaques that are involved in the progression of AD. In this article, we have provided a detailed chronological review of the research work on the BACE1 inhibiting potency of both flavonoids and chalcones. Almost all the flavonoids and chalcones mentioned in this article have shown very good in vitro and in vivo BACE1 inhibiting activity. The docking studies and the structural importance of some BACE1-inhibiting flavonoids, as well as chalcones, are also mentioned here.

Effects of intestine-specific deletion of FGF15 on the development of fatty liver disease with vertical sleeve gastrectomy.

Vertical sleeve gastrectomy (SGx) is a type of bariatric surgery to treat morbid obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). The molecular mechanisms of SGx to improve MASLD are unclear, but increased bile acids (BAs) and FGF19 (mouse FGF15) were observed. FGF15/19 is expressed in the ileum in response to BAs and is critical in not only suppressing BA synthesis in the liver but also promoting energy expenditure. We hypothesized the reduction of obesity and resolution of MASLD by SGx may be mediated by FGF15/19. First, we conducted hepatic gene expression analysis in obese patients undergoing SGx, with the results showing increased expression of FGF19 in obese patients' livers. Next, we used wild-type and intestine-specific Fgf15 knockout mice (Fgf15ile-/-) to determine the effects of FGF15 deficiency on improving the metabolic effects. SGx improved metabolic endpoints in both genotypes, evidenced by decreased obesity, improved glucose tolerance, and reduced MASLD progression. However, Fgf15ile-/- mice showed better improvement compared to wild-type mice after SGx, suggesting that other mediators than FGF15 are also responsible for the beneficial effects of FGF15 deficiency. Further gene expression analysis in brown adipose tissue suggests increased thermogenesis. FGF15 deficiency, the larger BA pool and higher levels of secondary BAs may increase energy expenditure in extrahepatic tissues, which may be responsible for improved metabolic functions following SGx.

Varicella zoster virus-induced autophagy in human neuronal and hematopoietic cells exerts antiviral activity.

Autophagy is a degradational pathway with pivotal roles in cellular homeostasis and survival, including protection of neurons in the central nervous system (CNS). The significance of autophagy as antiviral defense mechanism is recognized and some viruses hijack and modulate this process to their advantage in certain cell types. Here, we present data demonstrating that the human neurotropic herpesvirus varicella zoster virus (VZV) induces autophagy in human SH-SY5Y neuronal cells, in which the pathway exerts antiviral activity. Productively VZV-infected SH-SY5Y cells showed increased LC3-I-LC3-II conversion as well as co-localization of the viral glycoprotein E and the autophagy receptor p62. The activation of autophagy was dependent on a functional viral genome. Interestingly, inducers of autophagy reduced viral transcription, whereas inhibition of autophagy increased viral transcript expression. Finally, the genotype of patients with severe ocular and brain VZV infection were analyzed to identify potential autophagy-associated inborn errors of immunity. Two patients expressing genetic variants in the autophagy genes ULK1 and MAP1LC3B2, respectively, were identified. Notably, cells of both patients showed reduced autophagy, alongside enhanced viral replication and death of VZV-infected cells. In conclusion, these results demonstrate a neuro-protective role for autophagy in the context of VZV infection and suggest that failure to mount an autophagy response is a potential predisposing factor for development of severe VZV disease.

MiR-449a: A Promising Biomarker and Therapeutic Target in Cancer and Other Diseases.

In the regulation of gene expression, epigenetic factors like non-coding RNAs (ncRNAs) play an equal role in genetics. The role of microRNAs (miRNAs), which are members of the ncRNA family, in post-transcriptional gene regulation is well-documented and has important implications for both normal and abnormal biological processes, such as angiogenesis, proliferation, survival, and apoptosis. The purpose of this study was to synthesize previous research on miR-449a by analyzing published results from various databases, as there have been a number of investigations on miR-449's potential involvement in the development of human disorders. Based on our findings, miR-449 is strongly dysregulated in a wide range of diseases, from various cancers to cardiovascular diseases, cognitive impairments, and respiratory diseases, and it may play a pivotal role in the development of these problems. In addition, miR-449a functions as a crucial regulator of the expression of several well-known genes, including E2F-3, BCL2, NOTCH1, and SOX4. This, in turn, modulates various pathways and processes related to cancer, including Notch, PI3K, and TGF-β, and contributes to the improvement of cancer drug sensitivity. Curiously, abnormalities in the expression of this miRNA may serve as diagnostic or prognostic indicators for distinguishing between healthy people and patients or to evaluate the survival rates for specific disorders. This article provides a synopsis of the current understanding of miR-449a's role in human disease development through its regulation of gene expression and the biological processes related to these genes and their linked processes. In addition, we have covered the topic of miR-449a's potential as a clinical feature (diagnosis and prognosis) indicator for a range of disorders, both neoplastic and non-neoplastic. In general, our goal was to gain a thorough comprehension of the numerous functions of miR-449a in different disorders.

Chronological and Biological Aging in Amyotrophic Lateral Sclerosis and the Potential of Senolytic Therapies

Amyotrophic Lateral Sclerosis (ALS) is a group of sporadic and genetic neurodegenerative disorders that result in losses of upper and lower motor neurons. Treatment of ALS is limited, and survival is 2–5 years after disease onset. While ALS can occur in younger individuals, the risk significantly increases with advancing age. Notably, both sporadic and genetic forms of ALS share pathophysiological features overlapping hallmarks of aging including genome instability/DNA damage, mitochondrial dysfunction, inflammation, proteostasis, and cellular senescence. This review explores chronological and biological aging in the context of ALS onset and progression. Age-related muscle weakness and motor unit loss mirror aspects of ALS pathology and coincide with peak ALS incidence, suggesting a potential link between aging and disease development. Hallmarks of biological aging, including DNA damage, mitochondrial dysfunction, and cellular senescence, are implicated in both aging and ALS, offering insights into shared mechanisms underlying disease pathogenesis. Furthermore, senescence-associated secretory phenotype and senolytic treatments emerge as promising avenues for ALS intervention, with the potential to mitigate neuroinflammation and modify disease progression.

A potential association between COVID-19 vaccination and development of alzheimer's disease.

The challenges of the COVID-19 pandemic extend to concerns about vaccine side effects, particularly potential links to neurodegenerative diseases such as Alzheimer's disease (AD). This study investigates the association between COVID-19 vaccination and the onset of AD and its prodromal state, mild cognitive impairment (MCI). A nationwide, retrospective cohort study leveraging data from the Korean National Health Insurance Service was conducted. The study, conducted in Seoul, South Korea, analyzed data from a random 50% sample of city residents aged 65 and above, totaling 558,017 individuals. Participants were divided into vaccinated and unvaccinated groups, with vaccinations including mRNA and cDNA vaccines. The study focused on AD and MCI incidences post-vaccination, identified via ICD-10 codes, using multivariable logistic and Cox regression analyses. Patients with vascular dementia or Parkinson's disease served as controls. Findings showed an increased incidence of MCI and AD in vaccinated individuals, particularly those receiving mRNA vaccines, within three months post-vaccination. The mRNA vaccine group exhibited a significantly higher incidence of AD (Odds Ratio [OR]: 1.225; 95% Confidence Interval [CI]: 1.025-1.464; p = 0.026) and MCI (OR: 2.377; CI: 1.845-3.064; p < 0.001) compared to the unvaccinated group. No significant relationship was found with vascular dementia or Parkinson's disease. Preliminary evidence suggests a potential link between COVID-19 vaccination, particularly mRNA vaccines, and increased incidences of AD and MCI. This underscores the need for further research to elucidate the relationship between vaccine-induced immune responses and neurodegenerative processes, advocating for continuous monitoring and investigation into the vaccines' long-term neurological impacts.

Ocular effects of eye cosmetic formulations

ABSTRACT Objective To study the ocular effects seen among eye cosmetic wearers in the Indian Population. Methods This cross sectional study was conducted on female participants who had fulfilled the inclusion and exclusion criteria. A detailed history was obtained and thorough ophthalmic evaluation was done. Mann Whitney U test was used. Statistical analysis was done using IBM SPSS. p < 0.05 was taken as the level of statistical significance. Results Among a total of 225 participants in our study, the mean age was 24.23 ± 1.8 which comprised of young student females. Majority of the females used one eye cosmetics with Kajal (n = 156) being the most predominant. Most frequently encountered symptom upon using eye cosmetics was watering from eyes and ocular pain was the least encountered symptom. Anterior segment examination showed- allergic conjunctivitis and meibomian gland dysfunction being the most and least predominant respectively. Our study highlights that Kajal predisposes the eyes to significant ocular morbidity with p = 0.039 for Dry Eye Disease, p = 0.041 for Allergic Conjunctivitis, p = 0.036 for conjunctival pigmentation. Prolonged use of such formulations for more than 4 times a week (p = 0.046) or even daily(p = 0.031)for a duration of either 1-5 years (p = 0.033) or greater than 5 years (p = 0.027) was found to be statistically significant in causing ocular signs. Non removal of eye cosmetics at the end of the day was significant in causing allergic conjunctivitis (p = 0.035) and conjunctival pigmentation (p = 0.021). Plain tap water has been found to be the least effective technique in the removal of such ocular cosmetics with a statistical significance of p = 0.031 in causing ocular signs. Conclusions Eye cosmetics are a significant contributor to the development of ocular surface diseases. Removal of products along with decreased usage seems to be a significant contributor in dampening unwanted adverse effects.

The Curious Role of PAI-1 in Severe Obstructive Sleep Apnea

Plasminogen activator inhibitor-1 (PAI-1) has a significant role in fibrinolysis, atherogenesis, cellular senescence, and chronic inflammation. OSA (obstructive sleep apnea) leads to increased PAI-1 levels and the development of cardiovascular disease (CVD). The aim of this study was to determine the effects of CPAP therapy on coagulation parameters and PAI-1 in patients with severe OSA. This prospective, controlled study enrolled 57 patients who were newly diagnosed with severe OSA, 37 of whom had had good CPAP adherence after 6 months of therapy (usage of the device for at least 4 h per night), and their data were analyzed. The analysis showed a statistically significant increase in D-dimer values before CPAP therapy (415 (316.5–537.5)) vs. after therapy (499 (327–652)), p = 0.0282, and a decrease in fibrinogen values (3.665 ± 0.752 before CPAP therapy vs. 3.365 ± 0.771 after therapy, p = 0.0075)). PAI-1 concentration values before and after CPAP therapy did not differ significantly (17.35 ± 7.01 ng/mL before CPAP therapy vs. 17.42 ± 6.99 ng/mL after therapy, p = 0.9367). This study shows a tendency for fibrinolytic capacity to improve in patients with OSA after CPAP therapy, although PAI-1 levels did not differ significantly.

Emergence of the brain-border immune niches and their contribution to the development of neurodegenerative diseases

Historically, the central nervous system (CNS) was regarded as ‘immune-privileged’, possessing its own distinct immune cell population. This immune privilege was thought to be established by a tight blood-brain barrier (BBB) and blood-cerebrospinal-fluid barrier (BCSFB), which prevented the crossing of peripheral immune cells and their secreted factors into the CNS parenchyma. However, recent studies have revealed the presence of peripheral immune cells in proximity to various brain-border niches such as the choroid plexus, cranial bone marrow (CBM), meninges, and perivascular spaces. Furthermore, emerging evidence suggests that peripheral immune cells may be able to infiltrate the brain through these sites and play significant roles in driving neuronal cell death and pathology progression in neurodegenerative disease. Thus, in this review, we explore how the brain-border immune niches may contribute to the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). We then discuss several emerging options for harnessing the neuroimmune potential of these niches to improve the prognosis and treatment of these debilitative disorders using novel insights from recent studies.

An Eye into the Aorta: The Role of Extracellular Matrix Regulatory Genes ZNF469 and PRDM5, from Their Previous Association with Brittle Cornea Syndrome to Their Novel Association with Aortic and Arterial Aneurysmal Diseases

The extracellular matrix is a complex network of proteins and other molecules that are essential for the support, integrity, and structure of cells and tissues within the human body. The genes ZNF469 and PRDM5 each produce extracellular-matrix-related proteins that, when mutated, have been shown to result in the development of brittle cornea syndrome. This dysfunction results from aberrant protein function resulting in extracellular matrix disruption. Our group recently identified and published the first known associations between variants in these genes and aortic/arterial aneurysms and dissection diseases. This paper delineates the proposed effects of mutated ZNF469 and PRDM5 on various essential extracellular matrix components, including various collagens, TGF-B, clusterin, thrombospondin, and HAPLN-1, and reviews our recent reports associating single-nucleotide variants to these genes’ development of aneurysmal and dissection diseases.

The investigation of the role of oral-originated Prevotella-induced inflammation in childhood asthma

Background and objectivesThe oral and gut microbiota play significant roles in childhood asthma pathogenesis. However, the communication dynamics and pathogenic mechanisms by which oral microbiota influence gut microbiota and disease development remain incompletely understood. This study investigated potential mechanisms by which oral-originated gut microbiota, specifically Prevotella genus, may contribute to childhood asthma etiology.MethodsOral swab and fecal samples from 30 asthmatic children and 30 healthy controls were collected. Microbiome composition was characterized using 16S rRNA gene sequencing and metagenomics. Genetic distances identified potential oral-originated bacteria in asthmatic children. Functional validation assessed pro-inflammatory properties of in silico predicted microbial mimicry peptides from enriched asthma-associated species. Fecal metabolome profiling combined with metagenomic correlations explored links between gut microbiota and metabolism. HBE cells treated with Prevotella bivia culture supernatant were analyzed for lipid pathway impacts using UPLC-MS/MS.ResultsChildren with asthma exhibited distinct oral and gut microbiota structures. Prevotella bivia, P. disiens, P. oris and Bacteroides fragilis were enriched orally and intestinally in asthmatics, while Streptococcus thermophilus decreased. P. bivia, P. disiens and P. oris in asthmatic gut likely originated orally. Microbial peptides induced inflammatory cytokines from immune cells. Aberrant lipid pathways characterized asthmatic children. P. bivia increased pro-inflammatory and decreased anti-inflammatory lipid metabolites in HBE cells.ConclusionThis study provides evidence of Prevotella transfer from oral to gut microbiota in childhood asthma. Prevotella’s microbial mimicry peptides and effects on lipid metabolism contribute to disease pathogenesis by eliciting immune responses. Findings offer mechanistic insights into oral-gut connections in childhood asthma etiology.

Non-coding RNAs and their potential exploitation in cancer therapy-related cardiotoxicity.

Life expectancy in cancer patients has been extended in recent years, thanks to major breakthroughs in therapeutic developments. However, this also unmasked an increased incidence of cardiovascular diseases in cancer survivors, which is in part attributable to cancer therapy-related cardiovascular toxicity. Non-coding RNAs (ncRNAs) have received much appreciation due to their impact on gene expression. NcRNAs, which include microRNAs, long ncRNAs and circular RNAs, are non-protein-coding transcripts that are involved in the regulation of various biological processes, hence shaping cell identity and behaviour. They have also been implicated in disease development, including cardiovascular diseases, cancer and, more recently, cancer therapy-associated cardiotoxicity. This review outlines key features of cancer therapy-associated cardiotoxicity, what is known about the roles of ncRNAs in these processes and how ncRNAs could be exploited as therapeutic targets for cardioprotection.

Immune signature and therapeutic approach of natural killer cell in chronic liver disease and hepatocellular carcinoma.

Natural killer (NK) cells are one of the key members of innate immunity that predominantly reside in the liver, potentiating immune responses against viral infections or malignant tumors. It has been reported that changes in cell numbers and function of NK cells are associated with the development and progression of chronic liver diseases (CLDs) including non-alcoholic fatty liver disease, alcoholic liver disease, and chronic viral hepatitis. Also, it is known that the crosstalk between NK cells and hepatic stellate cells plays an important role in liver fibrosis and cirrhosis. In particular, the impaired functions of NK cells observed in CLDs consequently contribute to occurrence and progression of hepatocellular carcinoma (HCC). Chronic infections by hepatitis B or C viruses counteract the anti-tumor immunity of the host by producing the sheddases. Soluble major histocompatibility complex class I polypeptide-related sequence A (sMICA), released from the cell surfaces by sheddases, disrupts the interaction and affects the function of NK cells. Recently, the MICA/B-NK stimulatory receptor NK group 2 member D (NKG2D) axis has been extensively studied in HCC. HCC patients with low membrane-bound MICA or high sMICA concentration have been associated with poor prognosis. Therefore, reversing the sMICA-mediated downregulation of NKG2D has been proposed as an attractive strategy to enhance both innate and adaptive immune responses against HCC. This review aims to summarize recent studies on NK cell immune signatures and its roles in CLD and hepatocellular carcinogenesis and discusses the therapeutic approaches of MICA/B-NKG2D-based or NK cell-based immunotherapy for HCC.

Liver disease in patients with transfusion-dependent β-thalassemia: The emerging role of metabolism dysfunction-associated steatotic liver disease

In this Editorial, we highlight the possible role that metabolism dysfunction-associated steatotic liver disease (MASLD) may play in the future, regarding liver disease in patients with transfusion-dependent β-thalassemia (TDBT). MASLD is characterized by excessive accumulation of fat in the liver (hepatic steatosis), in the presence of cardiometabolic factors. There is a strong correlation between the occurrence of MASLD and insulin resistance, while its increased prevalence parallels the global epidemic of diabetes mellitus (DM) and obesity. Patients with TDBT need regular transfusions for life to ensure their survival. Through these transfusions, a large amount of iron is accumulated, which causes saturation of transferrin and leads to the circulation of free iron molecules, which cause damage to vital organs (primarily the liver and myocardium). Over the past, the main mechanisms for the development of liver disease in these patients have been the toxic effect of iron on the liver and chronic hepatitis C, for which modern and effective treatments have been found, resulting in successful treatment. Additional advances in the treatment and monitoring of these patients have led to a reduction in deaths, and an increase in their life expectancy. This increased survival makes them vulnerable to the onset of diseases, which until recently were mainly related to the non-thalassemic general population, such as obesity and DM. There is insufficient data in the literature regarding the prevalence of MASLD in this population or on the risk factors for its occurrence. However, it was recently shown by a study of 45 heavily transfused patients with beta-thalassemia (Padeniya et al , BJH), that the presence of steatosis is a factor influencing the value of liver elastography and thus liver fibrosis. These findings suggest that future research in the field of liver disease in patients with TDBT should be focused on the occurrence, the risk factors, and the effect of MASLD on these patients.

Autoimmune manifestations following COVID-19 infection in two individuals with primary immunodeficiency

Background: Due to widespread vaccination efforts worldwide, the mortality rates linked to COVID-19 have been decreasing. Nevertheless, there persists a notable level of morbidity, marked by increased occurrences of post-COVID-19 conditions. This includes the development of new autoimmune and inflammatory diseases in individuals who have recovered from COVID-19. A more severe progression of COVID-19 has been correlated with an increased probability of newly diagnosed autoimmune disease, and among individuals with preexisting autoimmune conditions, COVID-19 increased the risk of developing another autoimmune disease by 23%. Methods: Our patients’ medical records were analyzed retrospectively, including their medical history. Results: We present two cases of primary immunodeficiency patients. One of them experienced the onset of new autoimmune symptoms, while the other had a worsening of her autoimmune condition following COVID-19 infection. Conclusion: Recognizing the potential connection between COVID-19 and autoimmune conditions is crucial for identifying symptoms promptly in primary immunodeficiency patients and ensuring timely treatment. Further research is required to comprehensively grasp the relationship between COVID-19 and the development of autoimmunity in this particular patient group. Statement of Novelty: In this paper, we present a novel exploration into the emergence of autoimmune manifestations in primary immunodeficiency patients subsequent to COVID-19 infection, through an analysis of two distinct case reports.

Celiac Disease: The Importance of Studying the Duodenal Mucosa-Associated Microbiota

There is increasing evidence indicating that changes in both the composition and functionality of the intestinal microbiome are closely associated with the development of several chronic inflammatory diseases, with celiac disease (CeD) being particularly noteworthy. Thanks to the advent of culture-independent methodologies, the ability to identify and quantify the diverse microbial communities residing within the human body has been significantly improved. However, in the context of CeD, a notable challenge lies in characterizing the specific microbiota present on the mucosal surfaces of the intestine, rather than relying solely on fecal samples, which may not fully represent the relevant microbial populations. Currently, our comprehension of the composition and functional importance of mucosa-associated microbiota (MAM) in CeD remains an ongoing field of research because the limited number of available studies have reported few and sometimes contradictory results. MAM plays a crucial role in the development and progression of CeD, potentially acting as both a trigger and modulator of the immune response within the intestinal mucosa, given its proximity to the epithelial cells and direct interaction. According to this background, this review aims to consolidate the existing literature specifically focused on MAM in CeD. By elucidating the complex interplay between the host immune system and the gut microbiota, we aim to pave the way for new interventions based on novel therapeutic targets and diagnostic biomarkers for MAM in CeD.